Each year, patients undergo a vast number of surgical procedures in the United States. Current data shows about twenty-seven million procedures are performed per year. Post-operative or surgical site infections (“SSIs”) occur in approximately two to three percent of all cases. This amounts to more than 675,000 SSIs each year.
Whenever a medical device is used in a surgical setting, a risk of infection is created. The risk of infection dramatically increases for invasive or implantable medical devices, such as intravenous catheters, arterial grafts, intrathecal or intracerebral shunts and prosthetic devices, which create a portal of entry for pathogens while in intimate contact with body tissues and fluids. The occurrence of SSIs is often associated with bacteria that colonize on the medical device. For example, during a surgical procedure, bacteria from the surrounding environment may enter the surgical site and attach to the medical device. Bacteria can use the implanted medical device as a pathway to surrounding tissue. Such bacterial colonization on the medical device may lead to infection and morbidity and mortality to the patient.
A number of methods for reducing the risk of infection associated with invasive or implantable medical devices have been developed that incorporate antimicrobial agents into the medical devices. Such devices desirably provide effective levels of antimicrobial agent while the device is being used. For example, medical devices may contain antibiotics such as β-lactam antibiotics, polypeptides and quinolones. However, medical devices containing an antibiotic can suffer loss of efficacy resulting from the low stability of the antibiotic and more significantly, the increasing emergence of antibiotic-resistant bacteria. For instance, although β-Lactam antibiotics are known to be efficacious against S. aureus, the bacterial species that is believed to be the most common cause of surgical infections, these antibiotics are ineffective against antibiotic-resistant bacteria such as MRSA (methicillin-resistant Staphylococcus aureus) and MRSE (methicillin-resistant Staphylococcus epidermidis).
One potential solution to this problem is to use a combination of antibiotic and non-antibiotic antimicrobial agents to destroy or inhibit the growth of antibiotic-resistant bacteria. In particular, it is beneficial if the non-antibiotic antimicrobial agent has a differing pattern of bioavailability and mode of action from the antibiotic agent. The use of a blend of antimicrobial agents with different modes of action is often desirable to achieve a broader spectrum of antimicrobial activity against various organisms, especially against antibiotic-resistant bacteria.
US20050192547 A1 describes combinations of an antiseptic and an antibiotic in medical devices. In particular, this reference describes the use of (i) minocycline, triclosan, and a bismuth salt; (ii) minocycline, a chlorhexidine compound, and a bismuth salt; and (iii) minocycline, benzalkonium chloride, and a bismuth salt to deter the formation of antibiotic-resistant organisms.
There have been no reports to date on the use of a combination of (a) a cationic surfactant derived from the condensation of fatty acids and esterified dibasic amino acids and (b) an antibiotic. For example, LAE and an antibiotic are used in combination, resulting in an enhanced antimicrobial activity against a broader spectrum of the organisms, especially antibiotic-resistant bacteria.